The REPLACE Registry for Cholbam® (Cholic Acid)

A Prospective, Observational, Non-Interventional, Post-Marketing, Patient Registry to Collect Data on Routine Clinical Care in Patients Treated With Cholbam® (Cholic Acid)

This is a prospective, observational, non-interventional patient registry study designed to document product safety and effectiveness outcomes for 10 years in patients treated with Cholbam, including those who have been using Cholbam for at least 30 days (existing users) and those who are first-time initiators of Cholbam.

Study Overview

• Status: Active, not recruiting
• Conditions: Bile Acid Synthesis Disorders
• Intervention / Treatment: Drug: Cholbam

Detailed Description

No experimental intervention is involved. Patients in the Registry undergo clinical assessments and receive care as determined by the patient's treating physician.

• Study Type: Observational
• Enrollment (Estimated): 55

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
  • California
    • Palo Alto, California, United States, 94305
      • Stanford School of Medicine
    • San Francisco, California, United States, 94158
      • UC San Francisco
  • Florida
    • Hollywood, Florida, United States, 33021
      • Kidz Pediatric Multispecialty Group
    • Jacksonville, Florida, United States, 32207
      • Nemours duPont Pediatrics Specialty Clinic
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Healthcare of Atlanta
    • Atlanta, Georgia, United States, 30342
      • Children's Center For Digestive Health
  • Indiana
    • Topeka, Indiana, United States, 46571
      • The Community Health Clinic
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Hospital for Children
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Office of Dr. Esperanza Font-Montgomery MD
    • Saint Louis, Missouri, United States, 63110
      • Washington University at St Louis
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
    • New York, New York, United States, 10032
      • Montefiore Medical Center
    • Rochester, New York, United States, 14642
      • Golisano Children's Hospital, URMC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Monroe-Carell Jr. Children's Hospital at Vanderbilt
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients with a diagnosis for which Cholbam is indicated are eligible for inclusion in the Registry.

Description

Inclusion Criteria:

1. Male and female patients, of any age.
2. The patient and/or the patient's parent/legal guardian is willing and able to provide signed informed consent, and the patient, if less than 18 years of age, is willing to provide assent as appropriate and in accordance with local regulatory, IRB, and EC requirements.
3. The patient has a diagnosis for which Cholbam is indicated.
4. The patient is or will be treated with Cholbam at the time of signing the informed consent form (ICF) (enrollment).

Exclusion Criteria:

1. Patients who, by judgement of the Investigator, will not be able to comply with the requirements of the protocol will be excluded

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Existing User; Patients who have been using Cholbam for at least 30 days	Drug: Cholbam; Cholbam prescribed according to the approved label.
New User; First-time initiators of Cholbam	Drug: Cholbam; Cholbam prescribed according to the approved label.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with worsening cholestasis	Worsening cholestasis will be identified by measuring direct total bilirubin concentration in blood and will be defined as a 25% increase from previous measurement if the total bilirubin is >1mg/dL.	10 Years
Number of participants with new-onset cholestasis	Patients with new-onset cholestasis will be identified by detecting abnormal direct bilirubin concentration >1mg/dL or direct bilirubin greater than 20% of the total bilirubin if total bilirubin is >5mg/dL.	10 Years
Number of participants with steatorrhea leading to poor growth	Steatorrhea leading to poor growth in children, which will be defined as a decrease in growth percentiles from the original percentile at enrollment to the registry study.	10 Years
Changes in serum levels of fat-soluble vitamins	Fat-soluble vitamin (A, D, E, K) deficiencies will be identified by comparing results from serum assays (Vitamin A: Retinol, Vitamin D: 250HD2 + 250HD3, Vitamin K: Serum Vitamin K, Vitamin E: Serum Vitamin E) for each vitamin with standard ranges.	10 Years
Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies	Neuropathic signs or symptoms related to fat-soluble vitamin deficiencies (peripheral neuropathy, cerebellar ataxia) will be assessed by the Investigator.	10 Years
Number of participants with growth failure	Growth failure that the physician judges to be attributable to malabsorption.	10 Years
Death	AEs and SAEs leading to death will be recorded. The relatedness of death to Cholbam or disease progression will be recorded.	10 Years
Adverse effects on pregnancy, pregnancy outcomes, and infant status	Adverse effects on pregnancy, pregnancy outcomes, and infant status will be recorded.	10 Years
All Adverse Events (AEs) and Serious AEs (SAEs)	All other AEs and SAEs will be collected.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Cholbam dosing regimens and reasons for any dose modifications or treatment discontinuations		10 years
Changes from baseline in weight	For patients aged 18 years of or less, these data will be converted into Z-scores based on the WHO growth standards for infants aged 0-2 years and the Centers for Disease Control and Prevention growth standards for children 2-20 years. Growth failure will be defined as a decrease in percentiles from the original percentile at entry point into the registry study.	10 years
Changes from baseline in length/height	For patients aged 18 years of or less, these data will be converted into Z-scores based on the WHO growth standards for infants aged 0-2 years and the Centers for Disease Control and Prevention growth standards for children 2-20 years. Some patients will be adult or will have achieved final height. Growth failure will be defined as a decrease in percentiles from the original percentile at entry point into the registry study.	10 years
Changes from baseline in head circumference in infants	For patients aged 18 years of or less, these data will be converted into Z-scores based on the WHO growth standards for infants aged 0-2 years and the Centers for Disease Control and Prevention growth standards for children 2-20 years. Growth failure will be defined as a decrease in percentiles from the original percentile at entry point into the registry study.	10 years
Age-appropriate developmental milestones in infants	Measured by WHO Motor Development Milestones	10 years
Changes in prothrombin time (PT)		10 years
Changes in international normalized ratio (INR)		10 years
Changes in albumin		10 years
Changes in bilirubin		10 years
Changes in direct bilirubin		10 years
Changes in alanine aminotransferase (ALT)		10 years
Changes in aspartate aminotransferase (AST)		10 years
Changes in gamma-glutamyl transferase (GGT)		10 years
Changes in alkaline phosphatase		10 years
Presence or absence of urinary bile acids and levels of bile acid intermediaries and urinary bile alcohol		10 years
All indications for which Cholbam has been prescribed	Description of all indications for which Cholbam has been prescribed	10 years

Collaborators and Investigators

• Sponsor: Mirum Pharmaceuticals, Inc.
• Investigators: Study Director: Sagar A Vaidya, MD, PhD, Vice President, Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2017
• Primary Completion (Estimated): July 1, 2038
• Study Completion (Estimated): July 1, 2039

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cholic Acid; Bile Acid Synthesis Disorder; Zellweger Spectrum Disorder; Peroxisomal Disorder; Cholbam; The REPLACE Registry
• Other Study ID Numbers: 031CHO15001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No